AB1465 CAUSAL RELATIONSHIPS BETWEEN PHYSICAL ACTIVITIES, LEISURE SEDENTARY BEHAVIORS, AND ADULT-ONSET STILL DISEASE OUTCOMES
Authors: J. Y. Chen, W. Li, Q. Feng, Y. Feng, Q. Yu, P. F. He, X. Li, S. X. Zhang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Adult-onset Still's disease (AOSD) is a characteristic non-familial, multi-genic systemic auto-inflammatory disorder, characterized by fever and joint pain [1]. Whether physical activities (PAs)/ leisure sedentary behaviors (LSBs) directly affect AOSD susceptibility is inconclusive. <h3>Objectives</h3> This study aimed to investigate the causal effects of PAs and LSBs on AOSD. <h3>Methods</h3> We performed a two-sample Mendelian randomization (MR) analysis to investigate the causality of 5 PAs and 4 LSBs with AOSD, of which PAs include accelerometer-base physical activity measurement (average acceleration) (n=91,084), moderate to vigorous physical activity levels (MVPA) (n=377,234), vigorous physical activity (VPA) (n=377,234), moderate physical activity 10+ minutes (n=440,266), vigorous physical exercise 10+ minutes (n=440,512) [2], and LSBs include the length of mobile phone use (n=456,972), time spent driving (n=310,555), time spent using computer (n=360,895) and time spent watching television (TV) (n=437,887). Genome-wide significant genetic instruments (p &lt; 5 × 10–8) for PAs and LSBs were extracted from European-descent genome-wide association studies (GWASs). And to satisfy the assumption that single-nucleotide polymorphisms (SNPs) were not related to outcomes, one SNP (rs2857693) was removed. The PLINK algorithm (r2 <0.001) was used to clump SNPs at linkage disequilibrium (LD). AOSD data was acquired from the UK Biobank database (1,486 cases, 359,708 control samples, from Neale lab). Inverse variance weighted (IVW) was selected as the primary method for MR analysis. The MR-Egger and weighted median were considered secondarily. Moreover, sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, leave-one-out analysis, and the funnel plot to evaluate for heterogeneity and pleiotropy. <h3>Results</h3> Only spent driving time was positively correlated with AOSD in LSBs (odds ratio (OR) =1.02, 95% confidence interval (CI):0.001-0.319, p=0.0004). The Cochran's Q statistic with the IVW method revealed no heterogeneity (p=0.43), and no pleiotropy was observed (p = 0.618). However, the IVW results of PAs were not statistically significant (p>0.05), so PAs were not associated with AOSD (Figure 1). <h3>Conclusion</h3> Our findings support the hypothesis that time spent driving increases the risk of AOSD, suggesting leisurely sedentary behaviors may increase the probability of AOSD. <h3>References</h3> [1] Gerfaud-Valentin M, Jamilloux Y, Iwaz J, Sève P. Adult-onset Still's disease. Autoimmun Rev. 2014 Jul;13(7):708-22. doi: 10.1016/j.autrev.2014.01.058. Epub 2014 Mar 19. PMID: 24657513. [2] Klimentidis YC, Raichlen DA, Bea J, Garcia DO, Wineinger NE, Mandarino LJ, Alexander GE, Chen Z, Going SB. Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE. Int J Obes (Lond). 2018 Jun;42(6):1161-1176. doi: 10.1038/s41366-018-0120-3. Epub 2018 Jun 13. PMID: 29899525; PMCID: PMC6195860. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.